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T Akiyoshi

Publications and source records attributed to T Akiyoshi.

At least 73 records · Page 4Linked to original sources
PubMed1996

The expression of costimulatory molecules CD80 and CD86 in human carcinoma cell lines: its regulation by interferon gamma and interleukin-10.

The costimulatory signal through CD80 or CD86 to its counterreceptor CD28 or CTLA-4 on T cells has been shown to play an important role in the induction of T-cell-mediated immunity against tumors. In the present study, we examined the expression of CD80 and CD86 in the cell lines derived from human gastric, esophageal and colorectal carcinomas at the mRNA level, by means of a reverse transcriptase/polymerase chain reaction analysis and, for their surface expression, using a flow-cytometric analysis with monoclonal antibodies (mAb). The expression of mRNA for CD80 or CD86 was detected in all 18 cell lines tested, except for CD86 on one cell line. The cells from 13 (72%) or 12 (67%) of these cell lines expressed the surface CD80 or CD86 molecule, detected with the respective mAb. The surface expression of CD80 or CD86 was increased in four to five of the six cell lines tested after a culture with interferon gamma (IFN gamma). In addition, the up-regulation of CD80 or CD86 expression by IFN gamma was inhibited by interleukin-10 (IL-10). These results indicated that, in the cell lines derived from human gastrointestinal carcinoma, both the costimulatory molecules CD80 and CD86 were detectable in the majority of the cell lines examined at the mRNA and protein levels, and could be regulated with the cytokine IFN gamma or IL-10.

Antigens, CD↗
PubMed1996

Apoptosis in antibody-dependent monocyte-mediated cytotoxicity with monoclonal antibody 17-1A against human colorectal carcinoma cells: enhancement with interferon gamma.

Antibody-dependent cell-mediated cytotoxicity (ADCC) has been considered to be one of the main effector mechanisms by which unconjugated monoclonal antibody (mAb) 17-1A can exert an antitumor effect in vivo. Since the apoptotic pathway as well as the necrotic pathway have been shown to be utilized in various cytotoxic effector mechanism, we investigated the role of apoptosis in ADCC mediated by monocytes (ADMC) using mAb 17-1A as an antibody and the human colorectal carcinoma cell line, COLO205, as target cells in vitro. The implications of the apoptosis during ADMC was demonstrated by means of both a DNA fragmentation assay and a TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay. Furthermore, interferon gamma (IFN gamma) was also found to enhance the induction of apoptosis significantly. The addition of superoxide dismutase did not reduce the level of the apoptosis, although superoxide anion (O2-) was observed to be produced. However, the release of tumor necrosis factor alpha (TNF alpha) was significantly enhanced during ADMC, while, in addition, apoptosis was significantly inhibited by the addition of anti-TNF alpha antibody. These findings indicated that apoptosis might be implicated in ADMC with mAb 17-1A, which was augmented by IFN gamma, while, in addition, TNF alpha may also be one of the major mediators of apoptosis.

Antibodies, Monoclonal↗
PubMed1996

Expression of MAGE genes in human colorectal carcinoma.

OBJECTIVE: The human genes MAGE-1 and -3 encode tumor-specific peptide antigens, which are recognized by autologous cytotoxic T lymphocytes. The antigens coded by those genes may be useful for cancer immunotherapy. There is, however, little information on the expression of these genes in human colorectal carcinomas. METHOD: The expression of MAGE-1, -2, and -3 genes in 54 pairs of tumor and corresponding normal tissue specimens of the colorectum was determined by means of reverse transcription polymerase chain reaction. The induction of MAGE-1, -2, -3, and -4 gene expression in eight colorectal carcinoma cell lines also was examined by use of a demethylating agent, 5-Aza-2'-deoxycytidine (DAC). RESULTS: The expression of MAGE genes was not recognized in normal colorectal tissues at all. In tumor tissue specimens, the expression of MAGE-1, -2, and -3 was recognized in 16 (30%), 15 (28%), and 11 (20%) patients, respectively. The expression was seen frequently in patients with liver metastasis (p < 0.01). Although MAGE-1 or -3 genes were not induced by DAC, MAGE-2 or -4 genes were induced in three of four MAGE-2 negative cell lines or three of seven MAGE-4 negative cell lines, respectively. CONCLUSIONS: The MAGE genes were expressed exclusively in tumor tissues of one third of patients with colorectal carcinoma. The identification of such tumor rejection antigens is considered to uncover a new possibility for the specific immunotherapy of colorectal carcinoma. The demethylating agent may increase the number of patients who might be candidates for MAGE-specific immunotherapy.

Antigens, Neoplasm↗
PubMed1996

A case of alpha-fetoprotein-producing gastric cancer showing an exogastric growth pattern.

A case of alpha-fetoprotein (AFP)-producing gastric cancer, which showed a huge abdominal mass due to an exogastric growth, is here described. A 69-year-old Japanese woman with a huge abdominal mass, measuring 22 x 15 cm in size, had a serum AFP level that was exceptionally high (155 x 10(3) ng/ml). CT, barium meal studies, and gastrointestinal fiberoscopy revealed a gastric tumor with an exogastric growth pattern. The patient underwent a partial gastrectomy. The histological examination revealed that the tumor consisted of anaplastic carcinoma with positive staining for AFP. Although no liver metastasis was observed at operation, she died of multiple liver metastases 8 weeks after the operation. A gastric cancer that shows both AFP production and an exogastric growth pattern is quite rare and may be virulent.

Aged↗
PubMed1996

Elongation factor 1 gamma mRNA expression in oesophageal carcinoma.

Elongation factor 1 gamma (EF1 gamma) is known to be a subunit of EF1, one of the G proteins that mediate the transport of aminoacyl tRNA to 80S ribosomes during translation. As little is known regarding the expression of EF1 gamma in human oesophageal carcinoma, this study looked at its expression using a northern blot analysis. Thirty six cases of oesophageal carcinoma and 15 oesophageal carcinoma cell lines were studied. The EF1 gamma mRNA overexpression at a level of twofold or more was seen in five (14%) of 36 carcinomatous tissues compared with the normal counterparts. All five overexpressed cases showed severe lymph node metastases compared with the non-overexpressed cases, and the difference was significant (p = 0.028). The stage of the disease of these five cases was far advanced compared with the nonoverexpressed cases (p = 0.012). All 15 oesophageal carcinoma cells expressed EF1 gamma mRNA relatively lower than the gastric or pancreatic carcinoma cell lines, in which EF1 gamma was originally isolated. As the expression of EF1 gamma mRNA could be detected even in the biopsy specimens, its overexpression in tumour tissue may provide preoperative useful information for predicting the aggressiveness of tumours.

Adult↗
PubMed1996

Matrix metalloproteinase-7 expression in gastric carcinoma.

BACKGROUND/AIMS: Matrix metalloproteinase-7 (MMP-7) belongs to the same family as matrix degrading metalloproteinase (MMPs) that may play an important part in cancer cell invasion and metastasis. This study reports on the MMP-7 mRNA expression level both in human gastric carcinomas and the normal gastric mucosa. METHODS: From fresh specimens of 47 surgical pairs of primary gastric carcinomas and corresponding normal tissue specimens, cDNA was obtained by reverse transcription (RT) and thereafter MMP-7 mRNAs were detected by means of a polymerase chain reaction. The tumour/normal (T/N) ratio of MMP-7 expression was calculated after correcting for glyceraldehyde-3-phosphate dehydrogenase as an internal control. RESULTS: The expression corrected levels of MMP-7 mRNA of the tumour was greater than that of the normal mucosa in 41 of 47 cases (87%). The 13 cases whose T/N ratio was more than 2.1 showed a deeper invasion of the gastric wall, and more frequent lymphatic or vascular permeations than the 34 cases whose T/N ratio was less than 2.0. An immunohistochemical study showed that MMP-7 was predominantly expressed in the cancer cells, weakly expressed in normal epithelial cells, and not expressed in the surrounding stromal cells. CONCLUSIONS: These findings suggest that the overexpression of MMP-7 may thus play an important part in tumour invasion in gastric carcinomas while, in addition, MMP-7 may also prove to be a useful marker for determining the biological aggressiveness of gastric carcinoma.

Aged↗
PubMed1996

High prevalence of T cell receptor D delta 2(D delta)J delta rearrangement in CD7-positive early T cell acute lymphoblastic leukemia.

We have studied the molecular characteristics of the T cell receptor (TcR) genes in 16 patients with CD7+ early T cell acute lymphoblastic leukemia (T-ALL), defined as being positive for CD7 but negative for CD3/4/8, myeloperoxidase (MPO), and CD19/20. Using gene analysis, rearrangement was demonstrated in one patient for immunoglobulin heavy chain (IgH) gene, five for TcR-beta gene, and four for TcR-gamma gene. Fifteen patients (94%) had rearranged band(s) involving the joining region of the TcR-delta chain gene. In nine cases these were the only rearrangements, whereas in six cases TcR-beta and/or TcR-gamma gene rearrangements were found as well. The D delta 2(D delta)J delta 1 rearrangement was demonstrated in 87.5% (14/16) of cases. D delta 2(D delta)J delta 3 was recognized in one patient, D delta 2D delta 3 was found in three, and V(D)DJ using only V delta 2 and V delta 3 was recognized in two patients. We found no V2D delta 3, V3D delta 3, or V1(D)DJ delta rearrangement patterns. Five of nine cases with DDJ delta were positive for cytoplasmic CD3 epsilon(CyCD3 epsilon). Our data suggest that DDJ delta joining occurs at an early stage during T cell differentiation, followed by rearrangements of V delta to the DDJ delta complex. Furthermore, our findings suggest that DDJ delta recombination occurs earlier than expression of CyCD3 epsilon protein products. DDJ delta rearrangements have never been observed in non-T cell malignancies, such as precursor-B-ALL or acute myeloid leukemia. Therefore, detection of DDJ delta rearrangement in the TcR-delta locus is a useful tool to establish lineage and clonality of leukemic cells in the most immature stages of T cell development.

Antigens, CD↗
PubMed1996

[Prognostic factors of colon cancer from a molecular biology standpoint].

It has been reported that several genes may be good indicators for determining biological behavior, including the prognosis, of colorectal cancers. We have summarized these reported genes, such as tumor suppressor gene, oncogenes, metastasis suppressor gene, adhesion molecules, growth factors, proteinases, and others, including microsatellite instability. Some of the genes such as p53, DCC, c-met, or matrix metalloproteinase are considered to be reliable for determining biological aggressiveness. We introduced several interesting genes which we are focusing using cDNA subtraction library analysis. We hope that these genes are well combined for best analysis of the biological behavior of colorectal cancers and use for practical clinical analysis. In addition, we hope that novel important genes indicative for prognosis will be found.

Chromosome Deletion↗
PubMed1996

[Clinical significance of genetic instability in gastrointestinal cancers].

We reviewed the clinical significance of genetic instability or replication error (RER) in human gastrointestinal carcinomas. The RER positive tumors are seen in about 10-30% of these carcinomas. The RER positive esophageal carcinomas tend to show unusual histologic subtypes such as adenocarcinoma or small cell carcinoma. The RER positive gastric carcinomas show no specific characteristics in our study while several investigators describe the high frequency of poorly differentiated adenocarcinomas of the higher frequency of advanced carcinomas. The RER positive colorectal carcinomas show a tendency to show poorly differentiation to occur in the proximal colon, to have no lymph node metastasis and to show good prognosis. Several candidate genes that may correlate with RER are shown.

Adenocarcinoma↗
PubMed1996

Expression of BAGE, GAGE, and MAGE genes in human gastric carcinoma.

The MAGE, BAGE, and GAGE genes code for distinct antigens that are recognized by autologous cytolytic T lymphocytes. We investigated the expression of these genes in both cell lines and surgical samples of gastric carcinoma, using reverse transcription-PCR. Furthermore, the induction of these genes by 5-aza-2'-deoxycytidine (DAC), a demethylating agent, was also examined in several cell lines. Of 11 cell lines, BAGE, GAGE1-6, GAGE1-2, MAGE-1, and MAGE-3 were detected in 7 (64%), 4 (36%), 3 (27%), 8 (73%), and 8 (73%) cell lines, respectively. After the in vitro treatment of the negative cell lines with DAC, the expression of these genes became positive in 46 to 91% of these cell lines. No expression of these genes was seen in any of the 57 samples of normal gastric tissue. In contrast, the tumor tissue samples expressed BAGE, GAGE1-6, GAGE1-2, MAGE-1, and MAGE-3 in 13 (23%), 9 (16%), 6 (11%), 25 (44%), and 23 (40%) tissue samples, respectively. Thus, at least one of these genes was expressed in 35 (61%) of 57 carcinomas. An analysis of the relationship between clinicopathological factors and the expression of these genes revealed that either BAGE or one of these genes was more frequently expressed in histologically intestinal-type than in diffuse-type carcinomas. Our results suggest that, because of the higher expression of these genes and the possible induction of these genes by DAC, patients with gastric carcinoma may, therefore, be potential candidates for tumor-specific immunotherapy directed against these antigens.

Aged↗
PubMed1995

Human esophageal carcinomas frequently express the tumor-rejection antigens of MAGE genes.

The human genes MAGE-1 and -3 encode melanoma peptide antigens that are recognized by autologous cytotoxic T lymphocytes. Tumors expressing MAGE genes are potential targets for cancer immunotherapy, because MAGE genes are expressed only in tumor tissue and not in any normal tissue except testis and placenta. However, little is known about MAGE gene expression in human esophageal carcinoma. The purpose of this study was therefore to analyze MAGE gene status in human esophageal carcinoma. We studied the expression status of these genes in 42 surgical samples and in 12 cell lines of human esophageal carcinoma using the reverse transcription polymerase chain reaction (RT-PCR). Various clinicopathological factors were also analyzed. No MAGE gene expression was seen in any of the 42 normal esophageal tissue specimens. In contrast, tumor tissue expressed MAGE-1, -2, and -3 in 26, 18 and 24 specimens, respectively. Thirty-three of 42 tumors expressed at least one MAGE gene. Significant clinicopathologic differences between the tumors were not observed, regardless of the presence or absence of MAGE gene expression. In cell lines, MAGE-1, -2, and -3 gene expression was recognized in 5, 4 and 4 cell lines, respectively. This study demonstrates that MAGE genes are frequently expressed in clinical samples as well as in cell lines of esophageal carcinoma. The identification of MAGE genes, therefore, may open up a new modality of treatment, namely specific immunotherapy, for patients with esophageal carcinoma.

Aged↗
PubMed1995

Microsatellite instability in multiple gastric cancers.

To better elucidate the role of genetic instability in the development of gastric cancer, microsatellite alterations were examined in a total of 30 gastric cancers that developed in 14 Japanese patients with multiple gastric cancers, which are considered to have possibly occurred under the same genetic background and in the same microenvironment of the stomach. Microsatellite instability (MSI) in multiple gastric cancers was recognized in 11 out of 14 cases (78.5%) and in 16 out of 30 cancers (53.3%). Eight out of 11 cases showing MSI exhibited a heterogeneity of microsatellite alterations. The incidence of microsatellite instability in the multiple gastric cancers cases was significantly higher than that in the solitary gastric cancer cases reported previously (20.8%: 5 out of 24 cases). These results suggested that (1) genetic instability plays a more important role in the development of multiple gastric cancers than in that of solitary gastric cancer and (2) the heterogeneity of MSI in multiple gastric cancers may not be a rare event, although the significance of the heterogeneity could not be clarified.

Adenoma↗
PubMed1995

Microsatellite instability in Japanese esophageal carcinoma.

Recent studies have shown that microsatellite instability (MSI) may play an important role in the development of various types of cancer. However, there have been only 2 reports describing MSI in esophageal carcinoma and the clinicopathologic significance of MSI in this malignancy has not yet been clarified. To better elucidate the role of genetic instability in the development of esophageal carcinoma, we investigated the presence of MSI in 32 cases of esophageal cancer using paired samples of fresh frozen tumor and normal tissue by a method based on the polymerase chain reaction. MSI was defined as occurring in tumors which showed altered banding patterns at one or more microsatellite loci. The incidence of MSI in esophageal carcinoma was 6 out of 32 patients. MSI was observed more frequently in cases with small-cell carcinoma (2 out of 2) than in cases with squamous-cell carcinoma (4 out of 29). No cases with adenocarcinoma or Barrett's metaplasia were included in our series. No significant correlations between MSI and other clinicopathologic parameters were observed. The present study suggests that (1) some Japanese esophageal carcinomas certainly correlate with DNA replication error, and (2) MSI may be more frequent in small-cell carcinoma of the esophagus than in squamous-cell carcinoma of the esophagus.

Aged↗
PubMed1995

Detection of cancer micrometastases in lymph nodes by reverse transcriptase-polymerase chain reaction.

There are few DNA-based studies that detect cancer micrometastases in lymph nodes. We have assayed for the specific detection of carcinoembryonic antigen (CEA)-expressing carcinoma cells in the lymph nodes of patients with gastrointestinal or breast carcinomas. A CEA-specific nested reverse transcriptase (RT)-PCR assay was optimized using limiting dilutions of a CEA-positive cancer cell line mixed with normal lymphocytes. The expression of CEA mRNA was studied in 100 carcinoma tissues, 75 normal mucosal tissues, and 15 lymph nodes from patients with cholelithiasis. Each of 117 lymph nodes from 13 patients with carcinoma was divided into two pieces: one was used for histological examination and the other for RT-PCR, and the results were compared. The sensitivity ratio was one CEA-expressing cancer cell detected in 1 x 10(5) normal lymphocytes. All carcinoma tissues and normal mucosal tissues expressed CEA mRNA, while no amplification was detected in any control lymph nodes. Thirty of 117 lymph nodes were histologically involved by carcinoma cells, and all of these yielded the expected product by RT-PCR. Of the remaining 87 histologically negative nodes, CEA mRNA was detected in 47 lymph nodes by RT-PCR. The positive rate increased from 26% by histological examination to 66% by RT-PCR. The assay by CEA-specific nested RT-PCR is not only sensitive but widely applicable for the detection of cancer micrometastases in lymph nodes. This method may lead to an earlier diagnosis and treatment of patients with subclinical lymph node metastasis.

Adult↗
PubMed1995

The overexpression of elongation factor 1 gamma mRNA in gastric carcinoma.

BACKGROUND: Elongation factor 1 gamma (EF1 gamma) has been isolated from a pancreatic cancer cell line, while the overexpression of EF1 gamma has also been observed in colorectal carcinomas and adenomas. There is, however, still little information on the expression of EF1 gamma in gastric carcinoma. METHODS: The authors examined the expression of EF1 gamma mRNA in 30 gastric carcinomas and their corresponding paired adjacent normal mucosae obtained during surgery while also examining 10 human digestive tract carcinoma cell lines using Northern blot hybridization. RESULTS: An overexpression was observed in 22 (73%) of 30 gastric carcinomas, relative to the corresponding normal tissue. In a clinicopathologic study, no relationship was observed between the overexpression of EF1 gamma mRNA and the histologic grading or depth of tumor invasion. However, 15 (68%) of 22 overexpressed cases were positive for vascular permeation, whereas only 1 of 8 nonoverexpressed cases was positive for vascular permeation, and the difference was significant (P < 0.05). Nine (90%) of 10 with more than a 10-fold overexpression relative to the corresponding normal tissue showed severe vascular permeation in the histologic specimens. Conversely, the expression of EF1 gamma was observed not only in the pancreatic and gastric carcinoma cell lines, but also in the hepatic, ileocecal, duodenal, and colon carcinoma cell lines. CONCLUSIONS: The overexpression of EF1 gamma mRNA was observed in both the gastric carcinoma tissue and in all the other cell lines examined. This probable correlation with vascular permeation in gastric carcinoma is thus considered to provide another piece of useful pathologic information.

Base Sequence↗
PubMed1995

Microsatellite instability in Japanese gastric cancer.

BACKGROUND: Recent studies have shown that microsatellites are unstable in various types of cancers, and such genetic instability at the microsatellite loci (microsatellite instability) has been considered to play an important role in the development of cancer. However, the clinicopathologic significance of microsatellite instability in gastric cancer has not been clarified. METHODS: To elucidate the role of genetic instability in the development of gastric cancer, the presence of microsatellite instability was examined in 25 cases of gastric cancer using fresh-frozen tumor-normal paired samples using a polymerase chain reaction (PCR)-based method. Microsatellite instability was defined as tumors that showed altered banding patterns at two or more microsatellite loci. RESULTS: The incidence of microsatellite instability in gastric cancer cases was 4 of 25 patients (16%) and 4 of 26 cancers (15%). A significantly high incidence of microsatellite instability was observed in both the elderly (P < 0.01) and in lymph node metastasis-negative patients (P < 0.05). All patients with gastric cancer showing microsatellite instability were negative for lymphatic or venous permeation. A statistically significant association of microsatellite instability with no lymphatic permeation was thus observed (P < 0.05). CONCLUSIONS: This study revealed infrequent lymph node metastasis and lymph vessel invasion in the patients with gastric cancer demonstrating microsatellite instability. Although the number of examined cases was small, these findings suggest that gastric cancer that shows microsatellite instability may thus behave in a less malignant manner.

Chromosome Banding↗
PubMed1995

Overexpression of matrix metalloproteinase-7 mRNA in human colon carcinomas.

BACKGROUND: Matrix metalloproteinase-7 (MMP-7) is a member of the family of matrix-degrading metalloproteinases (MMPs) that are considered to contribute to cancer invasion and metastasis. One of the gene products that the authors have isolated by a cDNA subtraction of human gastric cancer minus normal gastric mucosa is MMP-7. The purpose of this study was to examine the expression of MMP-7 mRNA in different stages of human colorectal carcinomas. METHODS: A subtracted complementary DNA library was generated from a paired sample of human gastric carcinoma minus normal gastric mucosa. Screening of the library clones determined that MMP-7 mRNA was overexpressed. The complementary DNA insert was then used as a probe to evaluate the expression in a larger number of surgical samples of human colorectal carcinomas by Northern hybridization. RESULTS: The mRNA signal was greater in the colorectal carcinoma than in paired adjacent normal colonic or rectal mucosa in 39 of 47 cases. The expression of MMP-7 mRNA in tumor tissues increased with increasing Dukes' stage (P < 0.05). The MMP-7 mRNA expression was greatest in the metastatic liver lesions. CONCLUSIONS: The findings imply that MMP-7 mRNA is overexpressed in human colorectal carcinomas and that MMP-7 may prove useful as a marker of biologic aggressiveness.

Adenocarcinoma↗